HealthWatch runs every other week as a regular Gazette feature where medical journalist Evra Taylor Levy and emergency physician Eddy Lang help make sense of sometimes contradictory medical research.

Millions of people around the world are taking, or at one time took, supplements of vitamins C, E or beta-carotene as a means of improving their health. Many would even swear by their perceived benefits. Can all those people be wrong?: Can consuming supplements actually increase your risk of death? This edition of Healthwatch takes a close look at the latest controversy about vitamins and longevity.

Vitamins have been around for decades and have been touted as important nutritional supplements that can offset the effects of a poor diet and can improve health.

The group of vitamins called antioxidants has received special attention, in part because of results from laboratory and animal studies that suggested that they can counter the effects of free radicals - compounds that can damage cells and promote aging and cancer.

Even early clinical studies in humans suggested genuine health benefits linked to their regular consumption. Fuelling the widespread belief that vitamin supplements are good for you is a multi-billion dollar "health product" industry supported by powerful marketing strategies.

Researchers with the Cochrane collaboration, an international organization for evidence-based research, set out recently to answer the question of whether the use of antioxidants in the form of vitamins A, C, E, beta-carotene (a precursor to vitamin A) and selenium can lead to longer lives in both healthy individuals and in those with a variety of chronic diseases.

The researchers reviewed 67 high-quality studies representing more than 230,000 subjects who were randomly given either an anti-oxidant supplement or a placebo, or nothing at all, and followed for an average of about three years.

Remarkably, instead of extended longevity, researchers reported an average overall increase in mortality during the study of 2.6 per cent for the antioxidant-takers. This translates into one out of 40 users of an antioxidant vitamin, over a three-year period, succumbing to a premature death.

The results were similar in healthy vitamin users and those with chronic illnesses.

Vitamin A carried the highest increased risk of premature death, followed by beta-carotene and then vitamin E. Vitamin C, on the other hand, had neither a positive nor negative effect on mortality, and the results for selenium were inconclusive. Of note, the dosages used in the various studies generally exceeded Health Canada's recommended daily allowances, and often to a significant degree.

A number of theories have been put forward to explain the harmful effects of these antioxidant supplements, but they remain speculative.

These disturbing findings were not entirely unexpected: A number of high-profile studies already have suggested that antioxidants increase one's risk of death from cancer or cardiovascular disease. Although media reports have played down the risks of increased mortality with antioxidant use, the results are actually quite troublesome. In comparison, the side effects that led to Vioxx being taken off the market were associated with a much smaller increased risk of heart attack, and without a measurable effect on mortality.

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Among the more troubling aspects of this controversy is that vitamin supplements are more difficult to regulate than prescription medications. Health Canada can issue warnings about the consumption of vitamin supplements, but it would be unusual and complicated to order these products off health store and pharmacy shelves.

How does one explain the conflicting evidence?

Consumers are understandably confused by this seemingly contradictory evidence. How can something that medical research once endorsed now be reported as not only being ineffective, but actually dangerous?

Essential to understanding this phenomenon is an appreciation of the hierarchy of research evidence. Certain kinds of studies are more likely to link cause and effect than others; thus, conflicting research is often a case of weak studies reaching different conclusions than stronger ones.

In an example of a weaker study, imagine a large group of vitamin takers who are followed for years and are found to live longer than average lives. One might ascribe this to the use of vitamins; however, the observed benefits might, alternatively, be related to the fact that vitamin users are generally more health conscious, and therefore eat better and exercise more, with the vitamins having nothing to do with the observed benefits. Yet "observational" studies like these informed our early understanding of vitamin benefits.

Only randomized controlled trials - experiments that assign at least two groups of patients to comparative strategies - can prove a causal link between something like vitamins and life expectancy, and thus occupy a higher rung in the hierarchy. This is because randomization ensures that all the distracting factors that might have an effect on the results, whether researchers are aware of them or not, are equally distributed in the study groups. This leads to the conclusion, in most instances, that any detected differences are actually the result of the experimental treatment, in this case, the use of vitamins.

At the top of the hierarchy as seen by many in the evidence-based medicine community are studies that pool all of the randomized trials that can address a specific question; these are known as systematic reviews. One of the major benefits of systematic reviews is that they allow us to see effects across multiple studies that may not be detectable in a single study. By doing this, systematic reviews allow researchers to see small but important differences that single studies may not detect, thereby yielding surprising results.

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So, what's the bottom line?

Stop taking supplements of vitamins A, E and beta-carotene, plain and simple. Multivitamins, on the other hand, which contain very low doses of antioxidants, are unlikely to be of concern. The antioxidant vitamin controversy is both a humbling and valuable learning experience, teaching us to be vigilant and critical of what we think we know.

The material provided in HealthWatch is designed for general educational purposes only and does not pertain to individual cases. The information included should not replace necessary medical consultations with your own doctor or medical professional.

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